Mutant K-Ras in Pancreatic Cancer: An Insight on the Role of Wild-Type N-Ras and K-Ras-Dependent Cell Cycle Regulation.

The development of K-Ras independence may explain the failure of targeted therapy for pancreatic cancer (PC). In this paper, active N as well as K-Ras was shown in all human cell lines tested. In a cell line dependent on mutant K-Ras, it was shown that depleting K-Ras reduced total Ras activity, while cell lines described as independent had no significant decline in total Ras activity. The knockdown of N-Ras showed it had an important role in controlling the relative level of oxidative metabolism, but only K-Ras depletion caused a decrease in G2 cyclins. Proteasome inhibition reversed this, and other targets of APC/c were also decreased by K-Ras depletion. K-Ras depletion did not cause an increase in ubiquitinated G2 cyclins but instead caused exit from the G2 phase to slow relative to completion of the S-phase, suggesting that the mutant K-Ras may inhibit APC/c prior to anaphase and stabilise G2 cyclins independently of this. We propose that, during tumorigenesis, cancer cells expressing wild-type N-Ras protein are selected because the protein protects cancer cells from the deleterious effects of the cell cycle-independent induction of cyclins by mutant K-Ras. Mutation independence results when N-Ras activity becomes adequate to drive cell division, even in cells where K-Ras is inhibited.

An Analysis of the COVID-19-Induced Flexible Grading Policy at a Public University.

To help students cope with the challenges of the COVID-19 pandemic, higher education institutions offered students flexible grading policies that blended traditional letter grades with alternative grading options such as the pass-fail or credit-no credit options. This study conducted an in-depth analysis of the flexible grading policy at a medium-sized university in the USA. We studied the differential selection of flexible grading options by course characteristics and students' sociodemographics and academic profiles between Spring 2020 and Spring 2021. We also examined the impacts of the policy on sequential courses. Our analysis utilized administrative and transcript data for undergraduate students at the study institution and employed a combination of descriptive statistics and regression models. The analysis revealed that the flexible grading policy was utilized differently depending on course characteristics, with core courses and subjects like mathematics, chemistry, and economics having higher rates of usage. Additionally, sociodemographic and academic profile factors led to varying degrees of utilization, with males, urban students, freshmen, and non-STEM majors using the policy more frequently. Furthermore, the analysis suggested that the policy may have disadvantaged some students as they struggled in subsequent courses after using the pass option. Several implications and directions for future research are discussed.

Self-reported cognitive impairments and quality of life in patients with gastrointestinal stromal tumor: Results of a multinational survey.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has long-term effects on survivor quality of life, but CRCI research on patients with gastrointestinal stromal tumor (GIST) is lacking. The aims of this study were to investigate CRCI and concomitant quality of life among patients with GIST. METHODS: An online survey was used to assess CRCI in adult patients with GIST using the validated Functional Assessment of Cancer Therapy-Cognitive-v.3. Age, education, demographically indexed IQ, general health, and quality of life factors (e.g., fatigue, emotional distress) were also assessed. The online survey was administered through five international GIST and sarcoma support organizations. RESULTS: Over the 3-month recruitment period, the survey was completed by 485 participants: mean age, 57.80 (SD, 11.51), median 5 years after diagnosis. A majority (63.91%) reported experiencing cognitive symptoms with a significant negative quality of life impact. Controlling for age, patients with GIST ≥5 years after diagnosis reported worse cognitive function than those <5 years after diagnosis (p < .05) but did not differ in educational level or IQ. Whereas longer term survivors were more likely to have been treated with tyrosine kinase inhibitor (TKI) therapies, there was no observed association of TKI therapy with self-reported cognitive impairments. CONCLUSIONS: A majority of GIST patients report cognitive symptoms that have a negative impact on quality of life, with longer term survivors (≥5 years) tending to report more cognitive impairments. Given the success of TKI therapy to substantially increase overall survival of patients with GIST, addressing CRCI in clinical practice may improve long-term GIST survivor function and quality of life.

Factors influencing utilization of cancer rehabilitation services among older breast cancer survivors in the USA: a qualitative study.

PURPOSE: Many older breast cancer survivors experience long-term disability due to cancer and cancer-related treatments. However, less than 20% of older breast cancer survivors utilize cancer rehabilitation services to address cancer-related disability. Further understanding of survivor experiences may reveal strategies to improve uptake cancer rehabilitation services in the USA. METHODS: Older breast cancer survivors were recruited from university-based registries, previous breast cancer research studies at our institution, community support groups, and geriatric oncology clinics. Participants completed a brief online survey to capture demographic and clinical characteristics. Semi-structured telephone-based interviews were recorded, transcribed, and thematically analyzed. Interviews facilitated conversation about access to rehabilitation and indications for cancer rehabilitation. RESULTS: Participants (n = 14) were, on average, 71 years old, primarily White, and an average of 36.5 months post-diagnosis. Five participants had formally received rehabilitation for a cancer-related concern. Participants described seven factors that influenced utilization of cancer rehabilitation services: (1) emerging awareness of disability; (2) coping styles; (3) comparison of cancer experience with others; (4) provider interaction; (5) perceptions of cancer diagnosis; (6) social support; and (7) cost of rehabilitation. CONCLUSIONS: Older breast cancer survivors consider multiple factors when determining utilization of cancer rehabilitation services. Development of shared decision-making tools addressing the seven described factors may enhance communication and referral to cancer rehabilitation services. Intervention research should adopt frameworks that enhance healthcare accessibility to improve relevance of intervention content and delivery features for older breast cancer survivors.

Health Care Providers' and Professionals' Experiences With Telehealth Oncology Implementation During the COVID-19 Pandemic: A Qualitative Study.

BACKGROUND: Rapid implementation of telehealth for cancer care during COVID-19 required innovative and adaptive solutions among oncology health care providers and professionals (HPPs). OBJECTIVE: The aim of this qualitative study was to explore oncology HPPs' experiences with telehealth implementation during the COVID-19 pandemic. METHODS: This study was conducted at Moffitt Cancer Center (Moffitt), an NCI (National Cancer Institute)-Designated Comprehensive Cancer Center. Prior to COVID-19, Moffitt piloted telehealth visits on a limited basis. After COVID-19, Moffitt rapidly expanded telehealth visits. Telehealth visits included real-time videoconferencing between HPPs and patients and virtual check-ins (ie, brief communication with an HPP by telephone only). We conducted semistructured interviews with 40 oncology HPPs who implemented telehealth during COVID-19. The interviews were recorded, transcribed verbatim, and analyzed for themes using Dedoose software (version 4.12). RESULTS: Approximately half of the 40 participants were physicians (n=22, 55%), and one-quarter of the participants were advanced practice providers (n=10, 25%). Other participants included social workers (n=3, 8%), psychologists (n=2, 5%), dieticians (n=2, 5%), and a pharmacist (n=1, 3%). Five key themes were identified: (1) establishing and maintaining patient-HPP relationships, (2) coordinating care with other HPPs and informal caregivers, (3) adapting in-person assessments for telehealth, (4) developing workflows and allocating resources, and (5) future recommendations. Participants described innovative strategies for implementing telehealth, such as coordinating interdisciplinary visits with multiple HPPs and inviting informal caregivers (eg, spouse) to participate in telehealth visits. Health care workers discussed key challenges, such as workflow integration, lack of physical exam and biometric data, and overcoming the digital divide (eg, telehealth accessibility among patients with communication-related disabilities). Participants recommended policy advocacy to support telehealth (eg, medical licensure policies) and monitoring how telehealth affects patient outcomes and health care delivery. CONCLUSIONS: To support telehealth growth, implementation strategies are needed to ensure that HPPs and patients have the tools necessary to effectively engage in telehealth. At the same time, cancer care organizations will need to engage in advocacy to ensure that policies are supportive of oncology telehealth and develop systems to monitor the impact of telehealth on patient outcomes, health care quality, costs, and equity.

Tumor immunogenomic signatures improve a prognostic model of melanoma survival.

BACKGROUND: Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT. METHODS: Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS. RESULTS: Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E-14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E-08). This association was not observed in low TMB patients. CONCLUSIONS: We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.

The ecological impacts of multiple environmental stressors on coastal biofilm bacteria.

Ecological communities are increasingly exposed to multiple interacting stressors. For example, warming directly affects the physiology of organisms, eutrophication stimulates the base of the food web, and harvesting larger organisms for human consumption dampens top-down control. These stressors often combine in the natural environment with unpredictable results. Bacterial communities in coastal ecosystems underpin marine food webs and provide many important ecosystem services (e.g. nutrient cycling and carbon fixation). Yet, how microbial communities will respond to a changing climate remains uncertain. Thus, we used marine mesocosms to examine the impacts of warming, nutrient enrichment, and altered top-predator population size structure (common shore crab) on coastal microbial biofilm communities in a crossed experimental design. Warming increased bacterial α-diversity (18% increase in species richness and 67% increase in evenness), but this was countered by a decrease in α-diversity with nutrient enrichment (14% and 21% decrease for species richness and evenness, respectively). Thus, we show some effects of these stressors could cancel each other out under climate change scenarios. Warming and top-predator population size structure both affected bacterial biofilm community composition, with warming increasing the abundance of bacteria capable of increased mineralization of dissolved and particulate organic matter, such as Flavobacteriia, Sphingobacteriia, and Cytophagia. However, the community shifts observed with warming depended on top-predator population size structure, with Sphingobacteriia increasing with smaller crabs and Cytophagia increasing with larger crabs. These changes could alter the balance between mineralization and carbon sequestration in coastal ecosystems, leading to a positive feedback loop between warming and CO2 production. Our results highlight the potential for warming to disrupt microbial communities and biogeochemical cycling in coastal ecosystems, and the importance of studying these effects in combination with other environmental stressors.

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions 2020 think tank.

The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI's emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.

Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition.

Immune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, > 60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line ICI or combination treatment, we tested 25 SNPs, associated with > 2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568-a risk variant for allergy, colitis and type 1 diabetes-was associated with increased anti-PD-1 response, with significance surpassing multiple testing adjustments (OR 0.26; 95% CI 0.12-0.53; p = 0.0002). This variant maps to a locus of established immune-related genes: IL2 and IL21. Our study provides first evidence that autoimmune genetic susceptibility may modulate ICI efficacy, suggesting that systematic testing of autoimmune risk loci could reveal personalized biomarkers of ICI response.

UHRF1 regulation of the Keap1-Nrf2 pathway in pancreatic cancer contributes to oncogenesis.

The cellular defence protein Nrf2 is a mediator of oncogenesis in pancreatic ductal adenocarcinoma (PDAC) and other cancers. However, the control of Nrf2 expression and activity in cancer is not fully understood. We previously reported the absence of Keap1, a pivotal regulator of Nrf2, in ∼70% of PDAC cases. Here we describe a novel mechanism whereby the epigenetic regulator UHRF1 suppresses Keap1 protein levels. UHRF1 expression was observed in 20% (5 of 25) of benign pancreatic ducts compared to 86% (114 of 132) of pancreatic tumours, and an inverse relationship between UHRF1 and Keap1 levels in PDAC tumours (n = 124) was apparent (p = 0.002). We also provide evidence that UHRF1-mediated regulation of the Nrf2 pathway contributes to the aggressive behaviour of PDAC. Depletion of UHRF1 from PDAC cells decreased growth and enhanced apoptosis and cell cycle arrest. UHRF1 depletion also led to reduced levels of Nrf2-regulated downstream proteins and was accompanied by heightened oxidative stress, in the form of lower glutathione levels and increased reactive oxygen species. Concomitant depletion of Keap1 and UHRF1 restored Nrf2 levels and reversed cell cycle arrest and the increase in reactive oxygen species. Mechanistically, depletion of UHRF1 reduced global and tumour suppressor promoter methylation in pancreatic cancer cell lines, and KEAP1 gene promoter methylation was reduced in one of three cell lines examined. Thus, methylation of the KEAP1 gene promoter may contribute to the suppression of Keap1 protein levels by UHRF1, although our data suggest that additional mechanisms need to be explored. Finally, we demonstrate that K-Ras drives UHRF1 expression, establishing a novel link between this oncogene and Nrf2-mediated cellular protection. Since UHRF1 over-expression occurs in other cancers, its ability to regulate the Keap1-Nrf2 pathway may be critically important to the malignant behaviour of these cancers.

A randomized trial of videoconference-delivered cognitive behavioral therapy for survivors of breast cancer with self-reported cognitive dysfunction.

BACKGROUND: Long-term chemotherapy-related cognitive dysfunction (CRCD) affects a large number of cancer survivors. To the authors' knowledge, to date there is no established treatment for this survivorship problem. The authors herein report results of a small randomized controlled trial of a cognitive behavioral therapy (CBT), Memory and Attention Adaptation Training (MAAT), compared with an attention control condition. Both treatments were delivered over a videoconference device. METHODS: A total of 47 survivors of female breast cancer who reported CRCD were randomized to MAAT or supportive therapy and were assessed at baseline, after treatment, and at 2 months of follow-up. Participants completed self-report measures of cognitive symptoms and quality of life and a brief telephone-based neuropsychological assessment. RESULTS: MAAT participants made gains in perceived (self-reported) cognitive impairments (P = .02), and neuropsychological processing speed (P = .03) compared with supportive therapy controls. A large MAAT effect size was observed at the 2-month follow-up with regard to anxiety concerning cognitive problems (Cohen's d for standard differences in effect sizes, 0.90) with medium effects noted in general function, fatigue, and anxiety. Survivors rated MAAT and videoconference delivery with high satisfaction. CONCLUSIONS: MAAT may be an efficacious psychological treatment of CRCD that can be delivered through videoconference technology. This research is important because it helps to identify a treatment option for survivors that also may improve access to survivorship services. Cancer 2016;122:1782-91. © 2016 American Cancer Society.

A cognitive behavioral intervention (HOBSCOTCH) improves quality of life and attention in epilepsy.

OBJECTIVE: Cognitive difficulties in epilepsy are common and add to disability beyond seizures alone. A self-management intervention targeting cognitive dysfunction was developed and assessed for whether it improves quality of life, objective memory, and mood in adults with epilepsy. METHODS: The HOme Based Self-management and COgnitive Training CHanges lives (HOBSCOTCH) program was developed to incorporate (1) psychoeducation, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem solving therapy. Adults aged 18-65 years with epilepsy (n=66) were randomized into 3 groups, to receive 8 weeks of HOBSCOTCH, with (H+) or without (H) additional working memory training on a commercial gaming device, or to a waitlisted control group. The primary outcome was quality of life (Quality of Life in Epilepsy scale, QOLIE-31) with secondary outcomes of objective cognition measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and depression (as measured by PHQ9 and NDDIE). RESULTS: Both intervention arms showed a significant improvement in quality of life, as compared with controls who demonstrated a decline in QOLIE-31 scores. There was significant improvement in objective cognitive performance among the intervention groups, most notably in attention, compared with the waitlisted controls. There was no significant change in depression scores. SIGNIFICANCE: The HOBSCOTCH program significantly improved quality of life and appeared to be an effective intervention to address cognitive dysfunction in adults with epilepsy. Further studies are needed to assess the generalizability and cost-effectiveness of this intervention.

MRI Ferromagnetic Detector System: Fatigue Study.

*Ferromagnetic detectors capable of alerting MRI operators to potentially lethal projectile risks have been proven to increase patient safety. What is less well known is how such benefits may change over time. *The staff was involved in the whole study as they were trained on the use of the system, asked to record events that alerted the detector, and participated in follow up conversations about the impact of the systems and concerns or questions. *While a metal detection system is capable of reducing the number of incidents in which metal objects are brought into the MRI suite, technologists do become fatigued with the alarms in an MRI system and do not always consciously hear it.

Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial.

BACKGROUND AND PURPOSE: Post-hoc, we hypothesized that over the recruitment period of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), increasing experience and improved patient selection with carotid stenting, and to a lesser extent, carotid endarterectomy would contribute to lower periprocedural event rates. METHODS: Three study periods with approximately the same number of patients were defined to span recruitment. Composite and individual rates of periprocedural stroke, myocardial infarction, and death rate were calculated separately by treatment assignment (carotid stenting/carotid endarterectomy). Temporal changes in unadjusted event rates, and rates after adjustment for temporal changes in patient characteristics, were assessed. RESULTS: For patients randomized to carotid stenting, there was no significant temporal change in the unadjusted composite rates that declined from 6.2% in the first period, to 4.9% in the second, and 4.6% in the third (P=0.28). Adjustment for patient characteristics attenuated the rates to 6.0%, 5.9%, and 5.6% (P=0.85). For carotid endarterectomy-randomized patients, both the composite and the combined stroke and death outcome decreased between periods 1 and 2 and then increased in period 3. CONCLUSIONS: The hypothesized temporal reduction of stroke+death events for carotid stenting-treated patients was not observed. Further adjustment for changes in patient characteristics between periods, including the addition of asymptomatic patients and a >50% decrease in proportion of octogenarians enrolled, resulted in practically identical rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial.

Holmium:YAG laser bronchoscopy ablation of benign and malignant airway obstructions: an 8-year experience.

Patients suffering from severe tracheobronchial obstruction are vulnerable to dyspnea, respiratory failure, obstructive pneumonia, and death. Treatment with a holmium:YAG laser, an alternative to the neodymium:YAG laser, may provide symptomatic relief. This is the largest case series to date describing the application of the holmium:YAG laser via bronchoscopy for benign and malignant obstructive disease. The data were retrospectively collected from 99 patients, with either benign or malignant tracheobronchial obstruction, who underwent 261 interventional bronchoscopy procedures in the operating room with laser ablation between January 2004 and November 2011. Categorical variables were analyzed with the chi-square and Fisher's exact tests as appropriate in contingency tables, whereas Student's t-test was performed for comparison of continuous variables. Patient follow-up was concluded on September 15, 2013. The holmium:YAG laser was used in 261 procedures performed on 99 patients with either benign or malignant disease. Symptomatic improvement was demonstrated in 90 % of all benign etiology cases and 77 % of all malignant etiology cases. Within the benign and malignant subgroups, improvement was dependent on anatomical location rather than etiology of the lesion. Complications occurred in 2.3 % of the procedures, with mortality in less than 1 % of procedures. Results confirm the usefulness and safety of the holmium:YAG laser in the treatment of patients with severe benign and malignant obstructive tracheobronchial obstructions. The holmium:YAG laser is an appealing alternative to the neodymium:YAG laser.

Tyrosine Protein Kinase SYK-Related Gene Signature in Baseline Immune Cells Associated with Adjuvant Immunotherapy-Induced Immune-Related Adverse Events in Melanoma.

PURPOSE: Immune checkpoint inhibition (ICI) shows benefits in adjuvant (AT) and neoadjuvant melanoma treatments. However, ICI frequently induces severe immune-related adverse events (irAE). Unlike metastatic disease, in which irAEs are a clinical trade-off for treatment that improves survival, the toxicity burden from ICI in the AT setting is a substantial clinical problem urging for irAE-predictive biomarkers. EXPERIMENTAL DESIGN: We assessed postsurgical, pre-ICI treatment peripheral CD4+ and CD8+ T cells from clinical trial patients (CheckMate 915) treated with AT nivolumab (n = 130) or ipilimumab/nivolumab (COMBO, n = 82). Performing RNA sequencing differential gene expression analysis, we tested baseline differences associated with severe (grades 3-5) irAEs and constructed an irAE-predictive model using least absolute shrinkage and selection operator-regularized logistic regression. RESULTS: The analysis of predicted protein-protein interactions among differentially expressed genes in peripheral CD4+ cells revealed significant enrichment of the spleen tyrosine kinase (SYK) pathway, associated with severe irAEs in COMBO-treated patients. This gene expression signature predicted severe-irAE COMBO patients (χ2P value = 0.001) with 73% accuracy and was independent of disease recurrence (P = 0.79). The irAE-predictive model incorporating this gene expression signature demonstrated 82% accuracy (χ2P value = 8.91E-06). CONCLUSIONS: We identified baseline gene expression differences in key immune pathways of peripheral blood T cells from COMBO-treated patients with grades 3 to 5 irAEs and defined a SYK-related gene signature correctly identifying ∼60% of COMBO-treated patients with grades 3 to 5 irAEs. This finding aligns with our previous work linking anti-CTLA4 irAEs with a germline variant associated with high SYK expression. This gene signature may serve as a baseline biomarker of severe grade 3 to 5 irAE risk, which is especially important in AT treatment.

The National Cancer Institute Clinical Trials Planning Meeting to Address Gaps in Observational and Intervention Trials for Cancer-Related Cognitive Impairment.

Cancer-related cognitive impairment (CRCI) is a broad term encompassing subtle cognitive problems to more severe impairment. CRCI severity is influenced by host, disease, and treatment factors and affects patients prior to, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a Clinical Trial Planning Meeting (CTPM) to review the state of the science on CRCI and to develop both Phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non-central nervous system (CNS) disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of CRCI, members of the SxQOL SC, patient advocates, representatives from all seven NCI Community Oncology Research Program (NCORP) Research Bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacologic and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three CTPM working groups (longitudinal studies and pharmacologic and behavioral intervention trials) convened for one year to discuss and report on top priorities and to design studies. The CTPM experts concluded sufficient data exist to advance Phase II/Phase III trials utilizing selected pharmacologic and behavioral interventions for the treatment of CRCI in the non-CNS setting with recommendations included herein.

Stenting versus endarterectomy for treatment of carotid-artery stenosis.

BACKGROUND: Carotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke. METHODS: We randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization. RESULTS: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85). CONCLUSIONS: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)